Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome.

OBJECT: The goal of this study was to perform a critical review of literature pertinent to low-grade gliomas of the cerebral hemisphere in adults and, on the basis of this review, to evaluate systematically the prognostic effect of extent of resection on survival and to determine if treatment-related guidelines could be established for patients in whom these tumors have been newly diagnosed. Quality of evidence for current treatment options, guidelines, and standards as well as methodological limitations were evaluated. METHODS: Several prognostic factors thought to affect outcome in patients with low-grade gliomas include the patient's age and neurological status, tumor volume and histological characteristics, and treatment-related variables such as timing of surgical intervention, extent of resection, postoperative tumor volume, and radiation therapy. Patient age and the histological characteristics of the lesion are generally accepted prognostic factors. Among treatment-related factors, timing and extent of resection are controversial because of the lack of randomized controlled trials addressing these issues and the difficulty in obtaining information from available studies that have methodological limitations. All English-language studies on low-grade gliomas published between January 1970 and April 2000 were reviewed. Thirty studies that included statistical analyses were further evaluated with regard to the prognostic effect of extent of resection. Of these 30 studies, those that included pediatric patients, unless adults were analyzed separately, were excluded from further study because of the favorable outcome associated with the pediatric age group. Also excluded were studies including pilocytic and gemistocytic astrocytomas, because the natural histories of these histological subtypes are significantly different from that of low-grade gliomas. Series in which there were small numbers of patients (< 75) were also excluded. Results for oligodendrogliomas are reported separately. Currently, for patients with low-grade glial tumors located in the cerebral hemisphere, the only management standard based on high-quality evidence is tissue diagnosis. All other treatment methods are practice options supported by evidence that is inconclusive or conflicting. The majority of published series that the authors identified had design-related limitations including a small study size, a small number of events (that is, deaths for survival studies), inclusion of pediatric patients, and/or inclusion of various histological types of tumors with different natural histories. Of the 30 series addressing the issue of timing and extent of surgery, almost all had additional design limitations. Methods used to determine the extent of resection were subjective and qualitative in almost all studies. Only five of the 30 series met the authors' criteria, and these studies are discussed in detail. CONCLUSIONS: Management of low-grade gliomas is controversial and practice parameters are ill defined. This is caused by limited knowledge regarding the natural history of these tumors and the lack of high-quality evidence supporting various treatment options. Although a prospective randomized study seems unlikely, both retrospective matched studies and prospective observational trials will improve the clinician's ability to understand the importance of various prognostic factors.

The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere.

BACKGROUND: We retrospectively analyzed preoperative and postoperative radiographic tumor volumes in 92 patients who underwent hemispheric glioblastoma multiforme operations (107) to determine the factors that affect time to tumor progression (TTP) and overall survival. METHODS: Quantification of tumor volumes was based on a previously described method involving computerized image analysis of contrast enhancing tumor on computerized tomography or magnetic resonance imaging scans. RESULTS: Among the variables analyzed, preoperative Karnofsky Performance Status (KPS) (p < 0.05), chemotherapy (p < 0.05), percent of resection (POR) (p < 0.001), and volume of residual disease (VRD) (p < 0.001) had a significant effect on TTP. Factors that affected survival were age (p < 0.05), preoperative KPS (p = 0.05), postoperative KPS (p < 0.005), POR (p < 0.0005), and VRD (p < 0.0001). Greater resections did not compromise the quality of life, and patients without any residual disease had a better postoperative KPS than those patients who received less than total resections. CONCLUSIONS: The extent of tumor removal and the amount of residual tumor volume, documented on postoperative imaging studies, are highly significant factors affecting the median time to tumor progression and median survival for patients with glioblastoma multiforme of the cerebral hemisphere.

Intraoperative imaging techniques in the treatment of brain tumors.

Despite significant advances in medical imaging techniques and their routine preoperative use, real-time intraoperative information regarding anatomy remains of indisputable importance to neurosurgeons. Intraoperative displacement of the brain tissue caused by surgical retraction or the resection cavity itself, as well as shift caused by cerebrospinal fluid leakage, may result in alteration of the surgical anatomy of the lesion and surrounding structures. Neurosurgical navigation methods are beneficial in providing accurate intraoperative information regarding the anatomy of the surgical field. Furthermore, interactive image guidance may decrease incision lengths, operating times, and postoperative morbidity. This review focuses on recent developments in neurosurgical navigational techniques that enable real-time anatomic visualization during brain tumor surgery.

Microvascular decompression in the surgical management of trigeminal neuralgia.

The pathophysiological mechanisms underlying trigeminal neuralgia are not clearly understood and several therapeutic modalities have been advocated. Microvascular decompression (MVD) is a widely used surgical approach for the decompression of the affected root entry zone (REZ) of the fifth cranial nerve. In this paper, we present our experience based on 32 patients with trigeminal neuralgia who were treated with MVD, and discuss the role of this procedure in the surgical management of trigeminal neuralgia. All patients had typical TN pain and had had previous medical management which was unsuccessful. Fourteen patients (44%) had been previously treated with other surgical procedures and had persisting pain at the time of admission. Preoperatively, computerized tomography was obtained in all patients; twelve patients (37.5%) were evaluated with magnetic resonance imaging. These neuroradiological studies revealed an asymmetrical vascular structure at the involved REZ in nine patients (28%). All patients underwent MVD, and a vascular loop causing compression on the REZ of the fifth cranial nerve was demonstrated in each case. No mortality was observed, and the only permanent morbidity was cerebellar infarction in one patient (3%). Symptoms disappeared in all patients in the early postoperative period, and only three recurrences (12%) were observed within the follow-up period (mean: 26 months).

Establishment and characterization of four human medulloblastoma-derived cell lines.

We have established four cell lines, UW228-1, UW228-2, UW228-3 and UW443, from two posterior fossa medulloblastomas. The three UW228 sublines originated from a tumor with a diploid DNA content, while the tumor of origin of UW443 was predominantly tetraploid. Both tumors displayed areas of immunopositivity for synaptophysin and glial fibrillary acidic protein. All four cell lines have been grown as monolayers in continuous culture for 50 to 200 passages, are not contact inhibited at high density, and form colonies in soft agar. The UW228 sublines are aneuploid, have similar modal chromosome numbers, similar chromosomal duplications and identical marker chromosomes, and display loss of heterozygosity for identical sequences at the distal end of chromosome 17p. UW443 is diploid and also shows loss of heterozygosity for a distal sequence on chromosome 17p. All lines are immunopositive for two or more neurofilament proteins, three lines (UW228-1, UW228-2 and UW443) are immunopositive for synaptophysin, and none are immunopositive for glial fibrillary acidic protein. The lines differ in sensitivity to the alkylating agents 1,3-bis(2-chloroethyl)-1-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. They also differ in dependence on the DNA repair protein O6-methylguanine-DNA methyltransferase for alkylating agent resistance and in levels of the DNA repair activities apurinic/apyrimidinic endonuclease and DNA polymerase beta. These properties establish UW228-1, UW228-2, UW228-3 and UW443 as four new, phenotypically distinct medulloblastoma-derived cell lines.

The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas.

BACKGROUND: To evaluate the role of radical resection for low grade cerebral hemisphere gliomas, the authors analyzed the preoperative and postoperative radiographic tumor volumes (computed tomography hypodensity, magnetic resonance imaging-T2 signal hyperintensity) in 53 patients. METHODS: Using a previously described method of computerized image analysis, the authors evaluated whether the percent of resection and volume of residual disease, postoperatively, influenced the incidence of recurrence, time to tumor progression, and histology of the recurrent tumor. Survival was not analyzed in this study. RESULTS: No recurrence was detected, regardless of percent of resection and volume of residual disease, in patients with preoperative tumor volumes less than 10 cm2 (mean follow-up, 41.7 months). Patients with tumors measuring 10-30 cm3 had an incidence of recurrence and time to tumor progression of 13.6% and 58 months, respectively, compared with tumors measuring greater than 30 cm3, which had an incidence of recurrence and time to tumor progression of 41.2% and 30 months, respectively (P = 0.016). All patients (n = 13) who underwent a 100% resection had a recurrence-free follow-up period (mean, 54 months). In the remaining patients (n = 40), as the percent of resection decreased, the incidence of recurrence increased along with a shorter time to tumor progression (P = 0.03). Patients with a volume of residual disease of greater than 10 cm3 had a higher incidence of recurrence (46.2%) and a shorter time to tumor progression (30 months) compared with patients with a tumor volume of residual disease of less than 10 cm3 (incidence of recurrence, 14.8% and time to tumor progression, 50 months) (P = 0.002). Forty-six percent of patients with a tumor volume of residual disease of more than 10 cm3 had a recurrence of higher histologic grade, and this was significantly more frequent than patients with a volume of residual disease less than 10 cm3 (3.7%) (P = 0.0009). Age, radiotherapy, and histologic subtype had no influence on recurrence patterns. CONCLUSION: For tumors greater than 10 cm3, the authors' data suggest that a greater percent of resection and a smaller volume of residual disease conveys a significant advantage, that is, terms of incidence of recurrence and the recurrent tumor phenotype, for patients with low grade cerebral hemisphere gliomas, compared with those who have a less aggressive resection or biopsy. While this may also be the case with tumors less than 10 cm3, further follow-up is necessary to determine the effect of surgery on recurrence patterns for this subset of patients.

Ventricular entry during resection of malignant gliomas: effect on intracranial cerebrospinal fluid tumor dissemination.

The ventricular system is not infrequently entered during the course of maximum cytoreductive surgery for high-grade supratentorial gliomas. It is unclear if ventricular entry during surgery and/or proximity of the tumor to the ventricular system affects cerebrospinal fluid (CSF) tumor dissemination or the patients' overall survival rate. The authors retrospectively reviewed hospital records and neuroradiological studies of 51 patients operated on at the University of Washington between 1987 and 1991. Inclusion in this study necessitated a pathological diagnosis of malignant glioma and the availability of preoperative and postoperative computerized tomography scans or magnetic resonance images. Patients were excluded from the study if they had radiographic evidence of ventricular entry or CSF tumor dissemination prior to referral to the authors' institution. The index operation was defined as the first operation at the University of Washington or (in those patients with ventricular entry) the operation in which the ventricle was entered. Patients were followed until time of death or, in the case of survivors, until February, 1992. The effect of both ventricular entry and the proximity of the tumor to the ventricular system on CSF tumor dissemination and survival rate was assessed using statistical survival methodology. There was no significant difference in time from diagnosis to the index operation between groups compared (Mann-Whitney U-test, p > 0.40). Cerebrospinal fluid dissemination was radiographically documented in 18 patients (35%) following the index operation. This occurrence was not significantly influenced by either ventricular entry during surgery (Mantel-Cox test, p = 0.13), the proximity of the tumor to the ventricular system (p = 0.63), or these two variables combined (p = 0.28). Survival rate following the index operation was not significantly affected by ventricular entry (p = 0.66), proximity of the tumor to the ventricular system (p = 0.61), or these two variable considered in combination (p = 0.44). However, survival rate was significantly decreased once CSF tumor dissemination had occurred (Cox model, p = 0.03).

Detection of proliferating cell nuclear antigen in gliomas and adjacent resection margins.

We describe a technique for estimating the number of proliferating cells in gliomas and adjacent resection cavities after tumor removal. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Anti-PCNA antibody staining provides a semiquantitative estimate of the number of proliferating cells found in fixed tissue embedded in paraffin. The extent of the staining of tumor cells of glioblastoma multiforme, anaplastic astrocytomas, low-grade gliomas, and other lesions of the brain with anti-PCNA antibody is correlated with the histological diagnosis. In addition, the labeling of the margins after resection of gliomas and other lesions with anti-PCNA antibody is also associated with the histological diagnosis of the lesion. This technique may be useful in estimating the "biological" extent of resection and in predicting the recurrence patterns of gliomas.

Nerve growth factor receptor expression in medulloblastomas and the potential role of nerve growth factor as a differentiating agent in medulloblastoma cell lines.

Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and nonneoplastic cell lines. In this study, our aim was to determine NGF receptor (NGFr) status in medulloblastoma specimens and cell lines and to investigate whether NGF could act as a potential differentiating agent for this common pediatric brain tumor. Paraffin-embedded tumor tissue from 10 patients with the diagnosis of medulloblastoma was retrospectively analyzed to determine the frequency of NGFr expression. Of the 10 tumor specimens evaluated, 4 were positive for NGFr; however, NGFr staining was confined to only 5 to 8% of the cells in a randomly scattered pattern. No colocalization was present with neuronal, glial, or vascular structures. In addition, two medulloblastoma cell lines established in our laboratory were also evaluated for NGFr. In this study, we also examined the effects of retinoic acid, 12-O-tetradecanoyl-phorbol-13-acetate, and NGF on medulloblastoma cell lines to evaluate their effect on morphological differentiation and NGFr expression. Although these agents failed to cause NGFr expression in our cell lines, morphological alteration was noticed in only one of the cell lines with retinoic acid. Therefore, because of the lack of de novo or induced NGFr expression, it is unlikely that NGF will be useful as a potential therapeutic differentiating agent for medulloblastomas.

The aid of computerized tomography in hemifacial spasm.

Although the physiopathological mechanisms causing hemifacial spasm are not clearly understood, it is generally accepted that the causative factor is compression of the facial nerve at its root exit zone. In this paper we present seven cases of hemifacial spasm which were studied by dynamic CT scanning in the preoperative period, and treated with microvascular decompression. We suggest that CT scanning has considerable diagnostic value in disclosing the asymmetrical vascular formation causing root exit zone compression and that microvascular decompression should be the treatment of choice in this condition.

Measurement of tumor resection volumes from computerized images. Technical note.

The authors describe a method for quantitation of the area and volume of the resection cavity in patients who have undergone surgery for brain tumors. Using a slide scanner and Image 1.27, a public domain program for the Apple Macintosh II computer, computerized tomography scans and magnetic resonance images can be digitized and analyzed for a particular region of interest, such as the area and volume of tumor on preoperative and postresection scans. Phantom scans were used to analyze the accuracy of the program and the program users. User error was estimated at 2%, program error was 4.5%. This methodology is proposed as a means of retrospectively calculating the extent of tumor resection.

Surgical considerations in patients with lumbar spinal root anomalies.

Lumbosacral nerve root anomalies are rare and can cause diagnostic confusion. In this report we present 12 patients with lumbar root anomalies. Emphasis is placed on preoperative neuroradiological evaluation and the surgical implications of these anomalies.

Expression of glial fibrillary acidic protein in human medulloblastoma cells treated with recombinant glia maturation factor-beta.

Medulloblastoma, a common pediatric brain tumor, is a primitive neuroectodermal tumor which often displays neuronal and/or glial characteristics. We have investigated the consequences of treating cell lines derived from a human medulloblastoma with glia maturation factor-beta (GMF-beta), a protein found in mammalian brain. GMF-beta promotes growth arrest and morphological alteration of cultured glioma and neuroblastoma cells. The proliferation of medulloblastoma cells was arrested 24-48 hr after exposure to human recombinant GMF-beta. During the same period, treated cells acquired a morphology similar to that of mature astrocytes. By 72 hr, all treated cells bound an antibody against glial fibrillary acidic protein (GFAP), a distinguishing biochemical feature of mature astrocytes. Immunoreactivity was accompanied by de novo expression of GFAP mRNA. Our observations are the first demonstration of the induction of morphological and biochemical characteristics of mature astrocytes in cultured medulloblastoma-derived cells by an exogenous factor.

Correlation between computed tomography and magnetic resonance imaging in diastematomyelia.

Preoperative neuroradiological evaluation of diastematomyelia cases is of vital importance in order to increase surgical success rate. This paper reports the neuroradiological data of diastematomyelia cases in the light of surgical findings, and discusses the efficacy of CT and MRI in the evaluation of patients with diastematomyelia.

Cerebral echinococcosis multilocularis. Case report.

Cerebral occurrence of Echinococcus multilocularis is very rare and there is no widely accepted therapeutical method. In this report we present a case with an intracranial mass lesion and a palpable hepatic mass, which appeared to be due to Echinococcus multilocularis in the histopathological examination.

Seizure outcome in children with hemispheric tumors and associated intractable epilepsy: the role of tumor removal combined with seizure foci resection.

Children harboring hemispheric tumors associated with intractable epilepsy were retrospectively reviewed to assess seizure outcome following tumor resection and electrocorticography-guided seizure foci removal. Thirteen (93%) of our patients have remained seizure-free, off anticonvulsants or on tapering doses, following surgery with a mean follow-up of 33 months. Fifteen of 16 (93%) seizure foci examined histologically were void of tumor infiltration. A review of the literature is provided regarding the controversy of tumor removal versus additional seizure foci removal at the time of tumor removal in providing optimal seizure control.